DAVID LI L A B O R A T O R Y O F M O L E C U L A R N E U R O B I O L O G Y

B O S T O N U N I V E R S I T Y S C H O O L O F M E D I C I N E

Nanoparticle Synthesis for Drug Delivery

Background

�  Natural barriers between circulatory system and nervous system ¡  Central nerves: Blood-Brain Barrier (BBB) ¡  Central cerebrospinal fluid (BCSFB) ¡  Peripheral nerves: Blood-Nerve Fiber Barrier (BNFB)

http://www.nature.com/nrmicro/journal/v6/n8/images/nrmicro1952-f1.jpg

http://www.ncbi.nlm.nih.gov/books/NBK27998/

Background

�  Many psychoactive drugs cannot be therapeutic ¡  Barrier impermeability ¡  Metabolism before reaching target ¡  Nonspecific perfusion

�  Demand for designer therapeutics that match drug with specific delivery system

http://onlinelibrary.wiley.com/store/10.1002/adhm.201200112/asset/image_m/mcontent.jpg?

v=1&s=f8eb048c9587c3381d5e668e982b716db134fc50

http://www.hindawi.com/journals/jdd/2012/915375.fig.003.jpg

What is Nanotechnology?

�  Nanotechnology is the manipulation of matter between the atomic and the cellular scale ¡  Technically 1-100nm in diameter, though can be larger ¡  Biomedical applications include visualization and drug

delivery

http://www.livenano.org/wp-content/uploads/2011/03/quantum-dots.jpg http://www.ecosox.com/nanoparticles.jpg

Relevance to Molecular Neurobiology

�  Advances in biomedical engineering can be applied to research and skills in a basic research lab ¡  Effective noninvasive delivery of drugs and other substances ¡  Visualization and quantification

�  Goal: Identify and explore biomaterials and drug delivery as they relate to molecular neurobiology

http://www.nature.com/nrn/journal/v10/n9/fig_tab/nrn2685_F2.html

Project Proposal

�  Drugs and large molecules can be delivered to the brain from an intravenous injection ¡  Nanoparticles can cross the BBB and degrade ¡  Current issues include specific uptake by the

reticuloendothelial system

http://images.medicinenet.com/images/illustrations/lung-stomach-spleen.jpg

Project Proposal

�  Two main goals ¡  Determine whether novel materials can be incorporated into

this nanoparticle structure for brain delivery ¡  Modify the particles for more efficient delivery to the brain

Possible Implications

Steroid and Drug Delivery

Alternative Alzheimer’s Model Neurogenesis Modulator Delivery

Reproducible Encapsulation

Reduce RES Uptake Modulate Drug Release Curve

Surfactant Characterization

Materials Science

Pharmacology

Steroid and Drug Delivery

�  Many neuroactive steroids are not viable for therapeutics ¡  Solubility ¡  Toxicity

�  Targeted nanoparticles provide an efficient vehicle for delivery

Neurogenesis Modulator Delivery

�  Neurogenesis can be altered and the effects on spatial memory over time analyzed ¡  Invasive injection of rotovirus into brain ¡  Ineffective intravenous or intraperitoneal delivery

�  Targeted nanoparticles can deliver large drugs or, with modification, genes

Alternative Alzheimer’s Model

�  Alzheimer’s disease is a common form of dementia ¡  No known cure ¡  Formation of plaques, cause or effect unknown ¡  Causes breakdown of BBB

�  Targeted nanoparticles can deliver amyloid to the brain, creating plaques and generating a new experimental model

http://www.sigmaaldrich.com/medium/structureimages/77/mfcd00056177.png